title: Association between inflammatory infiltrates and isolated monosomy 22/del(22q) in meningiomas.
abstract: Meningiomas contain highly variable levels of infiltrating tissue macrophages (TiMa) and other immune cells. In this study we investigated the potential association between the number and immunophenotype of inflammatory and other immune cells infiltrating the tumor as evaluated by multiparameter flow cytometry, and the clinico-biological, cytogenetic and gene expression profile (GEP) of 75 meningioma patients. Overall, our results showed a close association between the amount and cellular composition of the inflammatory and other immune cell infiltrates and the cytogenetic profile of the tumors. Notably, tumors with isolated monosomy 22/del(22q) showed greater numbers of TiMa, NK cells and (recently)-activated CD69(+) lymphocytes versus meningiomas with diploid and complex karyotypes. In addition, in the former cytogenetic subgroup of meningiomas, tumor-infiltrating TiMa also showed a more activated and functionally mature phenotype, as reflected by a greater fraction of CD69(+), CD63(+), CD16(+) and CD33(+) cells. GEP at the mRNA level showed a unique GEP among meningiomas with an isolated monosomy 22/del(22q) versus all other cases, which consisted of increased expression of genes involved in inflammatory/immune response, associated with an M1 TiMa phenotype. Altogether, these results suggest that loss of expression of specific genes coded in chromosome 22 (e.g. MIF) is closely associated with an increased homing and potentially also anti-tumoral effect of TiMa, which could contribute to explain the better outcome of this specific good-prognosis cytogenetic subgroup of meningiomas.
authors.affiliation: Centre for Neurosciences and Cell Biology and Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal ; Centre for Cancer Research (CIC-IBMCC; CSIC/USAL; IBSAL) and Department of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: Patrícia Henriques
authors.initials: PH
authors.lastname: Domingues
authors.forename: Cristina
authors.initials: C
authors.lastname: Teodósio
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Otero
authors.forename: Pablo
authors.initials: P
authors.lastname: Sousa
authors.forename: Javier
authors.initials: J
authors.lastname: Ortiz
authors.forename: María del Carmen García
authors.initials: Mdel C
authors.lastname: Macias
authors.forename: Jesús María
authors.initials: JM
authors.lastname: Gonçalves
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Nieto
authors.forename: María Celeste
authors.initials: MC
authors.lastname: Lopes
authors.forename: Catarina
authors.initials: C
authors.lastname: de Oliveira
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Tabernero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000938:Antigen-Presenting Cells / Q000276:immunology; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D059785:Karyotype; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000276:immunology*; D008579:Meningioma / Q000235:genetics* / Q000276:immunology*; D008875:Middle Aged; D059467:Transcriptome; D055815:Young Adult